The objectives of this research are to determine the structural relationships between the active site and effector-molecule site of both Escherichia coli and HeLa glutamine synthetases. The methods that will be used involve nuclear magnetic resonance, nmr, measurements of relaxation rates of nuclei (13C, 31P, 1H, 15N) of substrates and inhibitor molecules; electron paramagnetic resonance, epr, measurements of bound Mn (II) will be used to detect changes in metal ion environment at the active site and inhibition sites; fluorescence energy transfer measurements between various fluorescent probes, will also be used to measure distances between metal ion sites, substrate sites, inhibitor binding sites and the adenylylation site of E. coli glutamine synthetase. These studies will be valuable for a fundamental understanding of the three-dimensional relationships among catalytic and effector molecule sites and how these geometric relationships serve to regulate enzymic activity. Knowledge of the control of glutamine synthetase in HeLa tumor cells, an enzyme central to all nitrogen metabolism in cells, may provide a molecular basis for understanding and controlling metabolism and growth of this carcinoma. Since the HeLa cell line supports the growth of many viruses, studies aimed at understanding the control of glutamine synthetase after viral infection may reveal changes in the control mechanisms for cellular nitrogen metabolism.